Dynorphin A (2–17) attenuates the unconditioned but not the conditioned effects of opiate withdrawal in the rat

Abstract.

Objectives: An unbiased place preference conditioning procedure was used to examine the influence of the non-opioid peptide, dynorphin A 2–17 (DYN 2–17), upon the conditioned and unconditioned effects of opiate withdrawal in the rat. Methods: Rats were implanted SC with two pellets containing 75 mg morphine or placebo. Single-trial place conditioning sessions with saline and the opioid receptor antagonist naloxone (0.1–1.0 mg/kg; SC) commenced 4 days later. Ten minutes before SC injections, animals received an IV infusion of saline or DYN 2–17 (0.1–5.0 mg/kg). Additional groups of placebo- and morphine-pelleted animals were conditioned with saline and DYN 2–17. During each 30-min conditioning session, somatic signs of withdrawal were quantified. Tests of place conditioning were conducted in pelleted animals 24 h later. Results: Naloxone produced wet-dog shakes, body weight loss, ptosis and diarrhea in morphine-pelleted animals. Morphine-pelleted animals also exhibited significant aversions for an environment previously associated with the administration of naloxone. These effects were not observed in placebo-pelleted animals. DYN 2–17 pretreatment resulted in a dose-related attenuation of somatic withdrawal signs. However, conditioned place aversions were still observed in morphine-pelleted animals that had received DYN 2–17 in combination with naloxone. Furthermore, the magnitude of this effect did not differ from control animals. Conclusions: These data demonstrate that the administration of DYN 2–17 attenuates the somatic, but not the conditioned aversive effects of antagonist-precipitated withdrawal from morphine in the rat. Differential effects of this peptide in modulating the conditioned and unconditioned effects of opiate withdrawal are suggested.